Studies On Enantioselective Liquid-liquid Extraction Of α-Amino Acids And Pantoprazole Enantiomers

The preparation of enantiopure compounds is of primary importance in the pharmaceutical and chemical industries. Enantioselective liquid-liquid extraction (ELLE) has attracted lots of attention for its operational simplicity and excellent economic efficiency. In this paper, ELLE is adopted to separate α-amino acids and pantoprazole enantiomers, the influence of process variales on extraction efficiency was studied experimentally. The extraction mechanisms were investigated and a reactive model was established. The main contents can be summarized as follows:In a-amino acids enantiomers separation part,(±)-2,2’-bis(diphenylphosphino)-1,1’-binaphthalene(BINAP) metal complexes were added into organic phase as chiral extractant. The separations of two kinds of a-amino acid enantiomers were studied in this part. And the effects of process variables such as types of organic solvents, pH, concentration of the extractant and temperature on extraction efficiency were investigated. Results show that for different kinds of a-amino acid enantiomers, process variables mentioned above have strong influence on different enantiomers. Considering BINAP metal complexes cannot be dissolved in aqueous phase, while a-amino acid enantiomers are highly hydrophilic, therefore, the interfacial reaction mechanism has been applied here and an interfacial reactive extraction model has been established. The models were then validated by comparison of the model predicitions with the experimental results. Models and optimizations based on the multivariate function were carried out to obtain the optimal extraction conditions and coefficients. Distribution ratios (kD and kL) of0.34and1.30, enantioselectivity (a) of3.86and enantiomeric excess (ee) of34.48%was achieved for Amino-(4-nitro-phenyl)-acetic acid(NPA). Distribution ratios (kDand kL) of1.98and0.54, enantioselectivity (a) of3.64and enantiomeric excess (ee) of29.94%was achieved for2-fluoro-phenylalanine (FPA). In pantoprazole separation part, biphasic chiral recognition system developed as an expansion of monophasic system, which combines a hydrophilic β-CD derivative in the aqueous phase and a hydrophobic tartaric acid ester in the organic phase. A number of factors which influence the efficiency of the extraction were investigated including types of organic solvents, β-CD and tartaric acid esters derivatives and their concentrations, pH and temperature. And a biphasic recognition extraction model has been established. The experimental results indicate that in biphasic system, the extraction performance is correlated with the recognition of both the β-CD derivative and the tartaric acid ester which preferentially recognise the (R)-enantiomer and (S)-enantiomer, respectively. And it is clear that the combined action of β-CD and tartaric acid esters leads to formation of the biphasic chiral extraction system with a stronger separation capacity than a monophasic chiral extraction system. And the most suitable extraction system for pantoprazole enantiomers was obtained by experiment. Organic solvents type, pH, concentration of extractant and temperature strongly influence on different enantiomers. As a result, distribution ratios(kR and ks) of2.22and1.56,enantioselectivity (a) of1.42and the enantiomeric excess (ee) of17.46%was achieved under optimised conditions.